类风湿关节炎小剂量甲氨蝶呤治疗药物监测及基因多态性研究进展
摘要
<正>类风湿关节炎(rheumatoid arthritis,RA)是以关节病变为主的慢性全身性炎症性疾病,累及全球约1%的人口,若未能早期有效控制可能致残,将严重影响患者的生活质量。每周1次小剂量(5～25mg)甲氨蝶呤(methotrexate,MTX)联合叶酸补充已经成为RA初始治疗的首选方案。近2/3的患者MTX单用或者联合应用即可达到治疗目标,但仍然
引文
[1] SAEVARSDOTTIR S,WALLIN H,SEDDIGHZADEH MA,et al. Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis:results from the initial open-label phase of the SWEFOT trial[J]. Ann Rheum Dis,2011,70(3):469
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[3] DERVIEUX T,FURST D,LEIN DO,et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier,aminoimidazole carboxamide ribonucleotide transformylase,and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis[J]. Arthritis Rheum,2004,50(9):2766
[4]DERVIEUX T,GREENSTEIN N,KREMER J. Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis[J]. Arthritis Rheum,2006,54(10):3095
[5] STAMP LK,ROBERTS RL. Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases[J]. Pharmacogenomics,2011,12(10):1449
[6] ANGELIS-STOFORIDIS P,VAJDA FJ,CHRISTOPHIDIS N. Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis[J]. Clin Exp Rheumatol,1999,17(3):313
[7] BECKER ML,VAN HAANDEL L,GAEDIGK R,et al. Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations[J]. Arthritis Rheum,2010,62(6):1803
[8] DALRYMPLE JM,STAMP LK,O'DONNELL JL,et al.Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis[J]. Arthritis Rheum,2008,58(11):3299
[9] BUDZIK GP,COLLETTI LM,FALTYNEK CR,et al.Effects of methotrexate on nucleotide pools in normal human T cells and the CEM T cell line[J]. Life Sci,2000,66(23):2297
[10]ROMAO VC,CANHAO H,FONSECA JE,et al. Old drugs,old problems:where do we stand in prediction of rheumatoid arthritis responsiveness to methotrexate and other synthetic DMARDs?[J]. BMC Med,2013,11:17
[11]SHEA B,SWINDEN MV,GHOGOMU ET,et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis[J]. Cochrane Database Syst Rev,2013(5):Cd000951
[12]VARANI K,PADOVAN M,GOVONI M,et al. The role of adenosine receptors in rheumatoid arthritis[J]. Autoimmun Rev,2010,10(2):61
[13]RAVANI A,VINCENZI F,BORTOLUZZI AA,et al. Role and Function of A(2A)and A(3)adenosine receptors in patients with ankylosing spondylitis,psoriatic arthritis and rheumatoid arthritis[J]. Int J Mol Sci,2017,18(4):697
[14]VARANI K,PADOVAN M,VINCENZI F,et al. A(2A)and A(3)adenosine receptor expression in rheumatoid arthritis:upregulation,inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release[J]. Arthritis Res Ther,2011,13(6):R197
[15]DERVIEUX T,FURST D,LEIN DO,et al. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate:results of a multicentred cross sectional observational study[J]. Ann Rheum Dis,2005,64(8):1180
[16]STAMP LK,O'DONNELL JL,CHAPMAN PT,et al. Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy[J]. Arthritis Rheum,2010,62(2):359
[17]STAMP LK,BARCLAY ML,O'DONNELL JL,et al. Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate polyglutamate concentrations and disease activity in patients with rheumatoid arthritis[J]. J Rheumatol,2011,38(12):2540
[18]HOBL EL,JILMA B,ERLACHER L,et al. A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid arthritis patients receiving methotrexate[J]. Clin Exp Rheumatol,2012,30(2):156
[19]ANDO Y,SHIMADA H,MATSUMOTO N,et al. Role of methotrexate polyglutamation and reduced folate carrier 1(RFC1)gene polymorphisms in clinical assessment indexes[J]. Drug Metab Pharmacokinet,2013,28(5):442
[20]DE ROTTE MC,DEN BOER E,DE JONG PH,et al. Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis[J]. Ann Rheum Dis,2015,74(2):408
[21]YAMAMOTO T,SHIKANO K,NANKI T,et al. Folylpolyglutamate synthase is a major determinant of intracellular methotrexate polyglutamates in patients with rheumatoid arthritis[J]. Sci Rep,2016,6:35615
[22]TAKAHASHI C,KANEKO Y,OKANO Y,et al. Association of erythrocyte methotrexate-polyglutamate levels with the efficacy and hepatotoxicity of methotrexate in patients with rheumatoid arthritis:a 76-week prospective study[J].RMD Open,2017,3(1):e000363
[23]LEE YC,CUI J,COSTENBADER KH,et al. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate[J]. Rheumatology(Oxford),2009,48(6):613
[24]LIMA A,MONTEIRO J,BERNARDES M,et al. Prediction of methotrexate clinical response in portuguese rheumatoid arthritis patients:implication of MTHFR rs1801133 and ATIC rs4673993 polymorphisms[J]. Biomed Res Int,2014,2014:368681
[25]OWEN SA,LUNT M,BOWES J,et al. MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis:analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms[J]. Pharmacogenomics J,2013,13(2):137
[26]SALAZAR J,MOYA P,ALTES A,et al. Polymorphisms in genes involved in the mechanism of action of methotrexate:are they associated with outcome in rheumatoid arthritis patients?[J]. Pharmacogenomics,2014,15(8):1079
[27]LOPEZ-RODRIGUEZ R,FERREIRO-IGLESIAS A,LIMA AA,et al. Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis[J]. Sci Rep,2018,8(1):7342
[28]HIDER SL,THOMSON W,MACK LF,et al. Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX[J].Rheumatology(Oxford),2008,47(8):1156
[29]VAN DER STRAATEN RJ,WESSELS JA,VRIES-BOUWSTRA VK,et al. Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients[J]. Pharmacogenomics,2007,8(2):141
[30]MOYA P,SALAZAR J,JESUS ARRANZ MA,et al. Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients[J]. Pharmacogenomics,2016,17(1):25
[31]LIMA A,BERNARDES M,AZEVEDO R,et al. Moving toward personalized medicine in rheumatoid arthritis:SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome[J]. Pharmacogenomics,2016,17(15):1649
[32]LIMA A,BERNARDES M,AZEVEDO R,et al. SLC19A1,SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in portuguese rheumatoid arthritis patients[J]. Toxicol Sci,2014,142(1):196
[33]LIMA A,BERNARDES M,SOUSA H,et al. SLC19A1 80G allele as a biomarker of methotrexate-related gastrointestinal toxicity in Portuguese rheumatoid arthritis patients[J].Pharmacogenomics,2014,15(6):807
[34]LIMA A,BERNARDES M,AZEVEDO R,et al. Pharmacogenomics of methotrexate membrane transport pathway:can clinical response to methotrexate in rheumatoid arthritis be predicted?[J]. Int J Mol Sci,2015,16(6):13760
[35]GOTTESMAN MM,FOJO T,BATES SE. Multidrug resistance in cancer:role of ATP-dependent transporters[J].Nat Rev Cancer,2002,2(1):48
[36]STAMP LK,O'DONNELL JL,CHAPMAN PT,et al. Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving longterm methotrexate treatment[J]. Arthritis Rheum,2009,60(8):2248
[2] GAUJOUX-VIALA C,RINCHEVAL N,DOUGADOS MA,et al. Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice:results from the ESPOIR early arthritis cohort[J]. Ann Rheum Dis,2017,76(12):2054
[3] DERVIEUX T,FURST D,LEIN DO,et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier,aminoimidazole carboxamide ribonucleotide transformylase,and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis[J]. Arthritis Rheum,2004,50(9):2766
[4]DERVIEUX T,GREENSTEIN N,KREMER J. Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis[J]. Arthritis Rheum,2006,54(10):3095
[5] STAMP LK,ROBERTS RL. Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases[J]. Pharmacogenomics,2011,12(10):1449
[6] ANGELIS-STOFORIDIS P,VAJDA FJ,CHRISTOPHIDIS N. Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis[J]. Clin Exp Rheumatol,1999,17(3):313
[7] BECKER ML,VAN HAANDEL L,GAEDIGK R,et al. Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations[J]. Arthritis Rheum,2010,62(6):1803
[8] DALRYMPLE JM,STAMP LK,O'DONNELL JL,et al.Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis[J]. Arthritis Rheum,2008,58(11):3299
[9] BUDZIK GP,COLLETTI LM,FALTYNEK CR,et al.Effects of methotrexate on nucleotide pools in normal human T cells and the CEM T cell line[J]. Life Sci,2000,66(23):2297
[10]ROMAO VC,CANHAO H,FONSECA JE,et al. Old drugs,old problems:where do we stand in prediction of rheumatoid arthritis responsiveness to methotrexate and other synthetic DMARDs?[J]. BMC Med,2013,11:17
[11]SHEA B,SWINDEN MV,GHOGOMU ET,et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis[J]. Cochrane Database Syst Rev,2013(5):Cd000951
[12]VARANI K,PADOVAN M,GOVONI M,et al. The role of adenosine receptors in rheumatoid arthritis[J]. Autoimmun Rev,2010,10(2):61
[13]RAVANI A,VINCENZI F,BORTOLUZZI AA,et al. Role and Function of A(2A)and A(3)adenosine receptors in patients with ankylosing spondylitis,psoriatic arthritis and rheumatoid arthritis[J]. Int J Mol Sci,2017,18(4):697
[14]VARANI K,PADOVAN M,VINCENZI F,et al. A(2A)and A(3)adenosine receptor expression in rheumatoid arthritis:upregulation,inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release[J]. Arthritis Res Ther,2011,13(6):R197
[15]DERVIEUX T,FURST D,LEIN DO,et al. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate:results of a multicentred cross sectional observational study[J]. Ann Rheum Dis,2005,64(8):1180
[16]STAMP LK,O'DONNELL JL,CHAPMAN PT,et al. Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy[J]. Arthritis Rheum,2010,62(2):359
[17]STAMP LK,BARCLAY ML,O'DONNELL JL,et al. Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate polyglutamate concentrations and disease activity in patients with rheumatoid arthritis[J]. J Rheumatol,2011,38(12):2540
[18]HOBL EL,JILMA B,ERLACHER L,et al. A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid arthritis patients receiving methotrexate[J]. Clin Exp Rheumatol,2012,30(2):156
[19]ANDO Y,SHIMADA H,MATSUMOTO N,et al. Role of methotrexate polyglutamation and reduced folate carrier 1(RFC1)gene polymorphisms in clinical assessment indexes[J]. Drug Metab Pharmacokinet,2013,28(5):442
[20]DE ROTTE MC,DEN BOER E,DE JONG PH,et al. Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis[J]. Ann Rheum Dis,2015,74(2):408
[21]YAMAMOTO T,SHIKANO K,NANKI T,et al. Folylpolyglutamate synthase is a major determinant of intracellular methotrexate polyglutamates in patients with rheumatoid arthritis[J]. Sci Rep,2016,6:35615
[22]TAKAHASHI C,KANEKO Y,OKANO Y,et al. Association of erythrocyte methotrexate-polyglutamate levels with the efficacy and hepatotoxicity of methotrexate in patients with rheumatoid arthritis:a 76-week prospective study[J].RMD Open,2017,3(1):e000363
[23]LEE YC,CUI J,COSTENBADER KH,et al. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate[J]. Rheumatology(Oxford),2009,48(6):613
[24]LIMA A,MONTEIRO J,BERNARDES M,et al. Prediction of methotrexate clinical response in portuguese rheumatoid arthritis patients:implication of MTHFR rs1801133 and ATIC rs4673993 polymorphisms[J]. Biomed Res Int,2014,2014:368681
[25]OWEN SA,LUNT M,BOWES J,et al. MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis:analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms[J]. Pharmacogenomics J,2013,13(2):137
[26]SALAZAR J,MOYA P,ALTES A,et al. Polymorphisms in genes involved in the mechanism of action of methotrexate:are they associated with outcome in rheumatoid arthritis patients?[J]. Pharmacogenomics,2014,15(8):1079
[27]LOPEZ-RODRIGUEZ R,FERREIRO-IGLESIAS A,LIMA AA,et al. Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis[J]. Sci Rep,2018,8(1):7342
[28]HIDER SL,THOMSON W,MACK LF,et al. Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX[J].Rheumatology(Oxford),2008,47(8):1156
[29]VAN DER STRAATEN RJ,WESSELS JA,VRIES-BOUWSTRA VK,et al. Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients[J]. Pharmacogenomics,2007,8(2):141
[30]MOYA P,SALAZAR J,JESUS ARRANZ MA,et al. Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients[J]. Pharmacogenomics,2016,17(1):25
[31]LIMA A,BERNARDES M,AZEVEDO R,et al. Moving toward personalized medicine in rheumatoid arthritis:SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome[J]. Pharmacogenomics,2016,17(15):1649
[32]LIMA A,BERNARDES M,AZEVEDO R,et al. SLC19A1,SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in portuguese rheumatoid arthritis patients[J]. Toxicol Sci,2014,142(1):196
[33]LIMA A,BERNARDES M,SOUSA H,et al. SLC19A1 80G allele as a biomarker of methotrexate-related gastrointestinal toxicity in Portuguese rheumatoid arthritis patients[J].Pharmacogenomics,2014,15(6):807
[34]LIMA A,BERNARDES M,AZEVEDO R,et al. Pharmacogenomics of methotrexate membrane transport pathway:can clinical response to methotrexate in rheumatoid arthritis be predicted?[J]. Int J Mol Sci,2015,16(6):13760
[35]GOTTESMAN MM,FOJO T,BATES SE. Multidrug resistance in cancer:role of ATP-dependent transporters[J].Nat Rev Cancer,2002,2(1):48
[36]STAMP LK,O'DONNELL JL,CHAPMAN PT,et al. Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving longterm methotrexate treatment[J]. Arthritis Rheum,2009,60(8):2248